In this thesis I scrutinized a specific region of the X chromosome of Drosophila melanogaster for evidence of positive directional selection. In addition, I analyzed the structure of six Southeast (SE) Asian populations of this species. In the first chapter, I analyzed a region that showed no polymorphism in a previous scan of the X chromosome in a European D. melanogaster population. This region, which I named the wapl region, is located on the distal part of the X chromosome, in cytological division 2C10 - 2E1. I observed a 60.5 - kb stretch of DNA encompassing the genes ph-d, ph-p, CG3835, bcn92, Pgd, wapl and Cyp4d1 that almost completely lacks variation in the European sample. Loci flanking this region show a skewed frequency spectrum at segregating sites, strong haplotype structure, and high levels of linkage disequilibrium. Neutrality tests revealed that these patterns of variation are unlikely under the neutral equilibrium model or simple bottleneck scenarios. In contrast, newly developed likelihood ratio tests suggest that strong positive selection has acted recently on the region under investigation, resulting in a selective sweep. Evidence is presented that this sweep may have originated in an ancestral population in Africa. In the second chapter, I revisited the center of the wapl region analyzed in chapter 1. I concentrated on the African D. melanogaster sample, as the valley of reduced variation found in the previous study was much narrower in the African sample than in the European one, which should help to pinpoint the target of selection. About 80% of the valley of reduced nucleotide variation was sequenced. This valley is located between the genes ph-d and Pgd. I therefore termed this part the ph-d - Pgd region. The new results confirm previous conclusions about selection having shaped nucleotide variability in this part of the D. melanogaster genome. Moreover, by sequencing the center of the selective sweep I was able to establish the haplotype structure in that region and to infer the historical context of the sweep. Most likely a positively selected substitution occurred at ph-p and was fixed before the out-of-Africa expansion of D. melanogaster, possibly >30,000 years ago. This substitution might be associated with the specialization of ph-p in gene regulation. In addition, the results obtained from the European sample indicate that sequence variation was not affected by demography alone. In fact, it was found that selection affected nucleotide diversity in the ph-d - Pgd region of the European sample as well. Since heterozygosity across the whole wapl region is substantially reduced, I propose that an additional selective sweep occurred at a different site in the European population. This is supported by an analysis regarding the time since the fixation of the (first) beneficial mutation at ph-p, which points toward a substitution in D. melanogaster before the colonization of Europe. In chapter 3, I obtained sequence data from six SE Asian samples for ten putatively neutrally evolving X-linked loci. Population genetic parameters were estimated and compared to those previously obtained from the European and the African sample. I observe substantially lower levels of nucleotide diversity in SE Asia than in either Africa or Europe. In particular, samples taken from more peripheral populations (e.g. Manila and Cebu, located on the Philippines) show a paucity of haplotypes. Common summary statistics indicate that genetic drift had a significant impact on these populations, which also led to considerable population substructure. One sample, i.e. Kuala Lumpur, however, shows rather high levels of heterozygosity among all SE Asian samples and is on average least differentiated from these. This indicates that the Kuala Lumpur population is ancestral to the other SE Asian populations, which is supported by a high amount of shared polymorphic sites. Finally, I revisited the wapl region, as analyzed in the first chapter, and find evidence that the selective sweep is older in Kuala Lumpur than in Europe.