Over this past decade, macroautophagy has gained prominence in the field of adult-onset neurodegeneration: from sporadic disorders such as Alzheimer's and Parkinson's disease, to genetic disorders such as Huntington's disease and frontotemporal dementia, the influence of this fundamental pathway has become an important topic of discussion. While there has been particular emphasis on the potential benefits of macroautophagy, there is growing literature that also suggests that macroautophagy contributes towards neurotoxicity. In this review, we discuss the molecular mechanism of macroautophagy and the currently available pharmacological tools, with special emphasis on mammalian macroautophagy in adult brain. Studies indicate that neuronal context strongly influences the role macroautophagy plays in maintaining cellular health, reflecting an ongoing need for better understanding of how macroautophagic regulation is achieved in the heavily differentiated and polarized neurons if we are to effectively manipulate it to treat neurodegenerative disease.