Programmed cell death eliminates unneeded and dangerous cells in a timely and effective manner during development. In this review, we examine the role cell death plays during development in worms, flies and mammals. We discuss signaling pathways that regulate developmental cell death, and describe how they communicate with the core cell death pathways. In most organisms, the majority of developmental cell death is seen in the nervous system. Therefore we focus on what is known about the regulation of developmental cell death in this tissue. Understanding how the cell death is regulated during development may provide insight into how this process can be manipulated in the treatment of disease.