Chaperone-mediated autophagy (CMA), a selective form of autophagy, where cellular proteins with KFERQ-like motif are targeted to the lysosome for degradation, is necessary to maintain cellular homeostasis. The role of CMA in neurodegenerative diseases has been extensively studied in the past decades, with defects in the pathway being strongly associated with disease. Recently, accumulating evidence has demonstrated a consistent increase in basal CMA activity in a wide array of cancer cell lines and human tumor biopsies, suggesting a potential link between CMA and cancer. On the other hand, an anti-oncogenic role for CMA under physiological conditions in non-transformed cells is also proposed despite the pro-tumorigenic function of CMA in cancer cells. The growing number of connections between CMA and cancers has generated interest in modulating CMA activity for therapeutic purposes. Here, we describe recent advances in the understanding of the molecular regulation of CMA, and discuss the evidence in support of the contribution of CMA dysfunction to cancers.