The most abundant homomeric nicotinic acetylcholine receptors (nAChRs) in the mammalian brain are the pentameric alpha7 nAChRs which consist of five alpha7 subunits, and each subunit provides an orthosteric low affinity binding site for its endogenous ligand, acetylcholine. Distribution and high level expression of alpha7 nAChRs within the limbic circuitry, including the hippocampus and prefrontal cortical areas are in line with their involvement in various cognitive functions. Activation of alpha7 nAChRs generates a conformational change of sub-unit proteins, making the channel permeable to cations, in particular calcium, leading to change in neuronal activity and excitability, and via increased intracellular calcium, modulating transmitter release and neuronal network activity. Since genetic linkage studies implicated the alpha7 nAChRs subunit gene CHRNA7 in schizophrenia, there is a considerable interest for developing drug therapies targeting alpha7 nAChRs. In this review recent development of selective agonists and positive allosteric modulators of alpha7 nAChRs are discussed. In addition to summarizing medicinal chemistry efforts, both cellular and neuronal network pharmacology of alpha7 nAChRs are covered. The association between CHRNA7 gene and impaired P50 auditory gating has provided an attractive endophenotype, and its use as a potential translational biomarker for alpha7 nAChRs drug discovery is discussed. Preliminary clinical findings on alpha7 nAChRs agonists are also summarized.