Angiopoietin-like proteins (ANGPTLs) are a family of proteins structurally similar to the angiopoietins. To date, eight ANGPTLs have been discovered, namely ANGPTL1 to ANGPTL8. Emerging evidence implies a key role for ANGPTLs in the regulation of a plethora of physiological and pathophysiological processes. Most of the ANGPTLs exhibit multibiological properties, including established functional roles in lipid and glucose metabolism, inflammation, hematopoiesis, and cancer. This report represents a systematic and updated appraisal of this class of proteins, focusing on the main features of each ANGPTL.