This review article focuses on the mechanisms of cellular uptake of cell-penetrating peptides (CPPs), which are short, positively charged peptides that can translocate through cell membranes to deliver large cargo molecules into cells. The authors discuss the two primary uptake mechanisms: endocytosis and direct penetration. Endocytosis involves the formation of endocytic vesicles, while direct penetration is an energy-independent process that can occur through various mechanisms such as pore formation, carpet-like perturbations, or inverted micelles. The review also highlights the importance of peptide structure, lipid composition, and experimental conditions in determining the uptake mechanism. Additionally, it explores the impact of cargo molecules and other factors on the cellular uptake of CPPs. The article concludes by discussing the similarities and differences between CPPs and antimicrobial peptides (AMPs), emphasizing their potential applications in drug delivery and cellular targeting.This review article focuses on the mechanisms of cellular uptake of cell-penetrating peptides (CPPs), which are short, positively charged peptides that can translocate through cell membranes to deliver large cargo molecules into cells. The authors discuss the two primary uptake mechanisms: endocytosis and direct penetration. Endocytosis involves the formation of endocytic vesicles, while direct penetration is an energy-independent process that can occur through various mechanisms such as pore formation, carpet-like perturbations, or inverted micelles. The review also highlights the importance of peptide structure, lipid composition, and experimental conditions in determining the uptake mechanism. Additionally, it explores the impact of cargo molecules and other factors on the cellular uptake of CPPs. The article concludes by discussing the similarities and differences between CPPs and antimicrobial peptides (AMPs), emphasizing their potential applications in drug delivery and cellular targeting.