Neurological diseases disrupt the quality of the lives of patients and often leads to their premature deaths. A common feature of most neurological diseases is the degeneration of neurons. It is generally accepted that neuronal loss, in these diseases, occurs by the inappropriate activation of a cell-suicide process called apoptosis. Drugs that inhibit neuronal apoptosis could thus be candidates for therapeutic intervention in neurodegenerative disorders. In this review we describe advances made in recent years on the molecules and signal transduction pathways that regulate neuronal apoptosis either positively or negatively. Emphasis is on molecules that are being targeted for the potential treatment of neurodegenerative conditions in humans. Furthermore, we will summarize results from studies performed using small-molecule neuroprotective drugs that target specific signaling molecules known to regulate neuronal apoptosis.