During normal nervous system development, physiologically appropriate neuronal apoptosis contributes to a sculpting process that removes approximately one-half of all neurons born during neurogenesis. However, neuronal apoptosis subsequent to this developmental window is physiologically inappropriate for most systems and can contribute to neurodegenerative diseases. Neuronal apoptosis is characterized by specific morphological events and requires the activation of an intrinsic transcriptional program. With the completion of genome sequencing in humans and model organisms, and the advent of DNA microarray technology, the transcriptional cascades and networks regulating neuronal apoptosis are being elucidated providing new potential pharmacological targets. This review will introduce the reader to this genomic approach and illustrate with a few examples a methodological strategy for the rational selection of pharmacological targets and the development of neuroprotective agents.