Ceramides are ubiquitous lipids that have important functions integral to apoptotic signaling. Several therapeutic agents currently exist that induce ceramide-dependent apoptosis in cancerous cells, and a number of enzymes involved in ceramide metabolism are beginning to be recognized as potential targets for cancer therapy. Recent research shows that evasion of ceramide-dependent apoptosis is essential at the earliest stages of embryonic development and is an important mechanism of multidrug resistance. Although ceramide-based strategies for treating cancer are promising, current data about ceramide-resistant tumors require further understanding of the role of ceramide in apoptosis.