Autophagy is a physiological and evolutionarily conserved phenomenon maintaining homeostatic functions like protein degradation and organelle turnover. It is rapidly upregulated under conditions leading to cellular stress, such as nutrient or growth factor deprivation, providing an alternative source of intracellular building blocks and substrates for energy generation to enable continuous cell survival. Yet accumulating data provide evidence that the autophagic machinery can be also recruited to kill cells under certain conditions generating a caspase-independent form of programed cell death (PCD), named autophagic cell death. Due to increasing interest in nonapoptotic PCD forms and the development of mammalian genetic tools to study autophagy, autophagic cell death has achieved major prominence, and is recognized now as a legitimate alternative death pathway to apoptosis. This chapter aims at summarizing the recent data in the field of autophagy signaling and autophagic cell death.