This review discusses the roles of PINK1 and Parkin in mitochondrial quality control and their implications in Parkinson's disease (PD). PINK1 accumulates on dysfunctional mitochondria, activating Parkin's E3 ubiquitin ligase activity and recruiting it to the mitochondria. Parkin ubiquitinates outer mitochondrial membrane proteins, triggering selective autophagy (mitophagy). The accumulation of PINK1 on damaged mitochondria is regulated by proteolysis and involves the TOM complex and LON protease. PINK1 also phosphorylates ubiquitin and Parkin, enhancing their activity. Parkin ubiquitinates various mitochondrial proteins, leading to their degradation or extraction from the outer membrane. The activation of Parkin by PINK1 and the subsequent ubiquitination of mitochondrial proteins form a positive feedback loop that ensures mitochondrial clearance. Genetic and pharmacological manipulations of the PINK1/Parkin pathway have been used to study its function in vivo, with varying degrees of success in modeling PD. Drosophila models of PINK1 and Parkin mutations have provided valuable insights into the genetic link between these proteins and mitochondrial integrity.This review discusses the roles of PINK1 and Parkin in mitochondrial quality control and their implications in Parkinson's disease (PD). PINK1 accumulates on dysfunctional mitochondria, activating Parkin's E3 ubiquitin ligase activity and recruiting it to the mitochondria. Parkin ubiquitinates outer mitochondrial membrane proteins, triggering selective autophagy (mitophagy). The accumulation of PINK1 on damaged mitochondria is regulated by proteolysis and involves the TOM complex and LON protease. PINK1 also phosphorylates ubiquitin and Parkin, enhancing their activity. Parkin ubiquitinates various mitochondrial proteins, leading to their degradation or extraction from the outer membrane. The activation of Parkin by PINK1 and the subsequent ubiquitination of mitochondrial proteins form a positive feedback loop that ensures mitochondrial clearance. Genetic and pharmacological manipulations of the PINK1/Parkin pathway have been used to study its function in vivo, with varying degrees of success in modeling PD. Drosophila models of PINK1 and Parkin mutations have provided valuable insights into the genetic link between these proteins and mitochondrial integrity.