Epileptogenesis and epilepsy progression are associated with rearrangements of neuronal circuits mediated by such processes as sprouting, neuronal cell death, and neurogenesis. These processes lead to hyperexcitability, spontaneous seizures, and/or worsening of seizure severity/frequency. Neurotrophic factors, and the Fibroblast Growth Factor-2 (FGF-2) in particular, are mediators for these reorganizational processes, and thus may play a role in epileptic phenomena. In this article, we will summarize and discuss the data supporting this hypothesis. Experimental evidence demonstrates that: 1) Seizures increase FGF-2 mRNA and protein levels in specific brain areas, and up-regulate the expression of the FGF-2 high-affinity receptor, FGFR-1; 2) Acute injection of FGF-2 causes seizures, while chronic infusion of low dose FGF-2 does not affect kainate-induced seizures but reduces hippocampal damage; 3) Kainate-induced seizure severity is not altered in FGF-2 knock-out mice, but is increased in FGF-2 over-expressing mice. Thus, FGF-2 may be implicated in seizure susceptibility and in seizure-induced plasticity, exerting two different, and apparently contrasting effects - favoring ictogenesis but reducing seizure-induced cell death. Dissecting out the mechanisms underlying these effects will be critical in pursuing the goal of controlling seizures and their deleterious consequences through modulation of the FGF-2 system.