Sialic acid-binding immunoglobulin-like lectins (Siglecs) are predominantly expressed in immune cells and exhibit distinct expression patterns depending on the Siglec family member. Many Siglecs function as inhibitory receptors, whereas some transmit activating signals. Through these functions, Siglecs regulate a wide range of biological processes involved in the development of various diseases. Regulation of various diseases. Siglec-7, -9, -10, and -15 modulate tumor immunity by acting as immune checkpoint molecules. CD22 (also known as Siglec-2) suppresses generation of regulatory B cells thereby regulating autoimmune diseases and transplantation immunity. In addition, certain Siglecs are expressed in tissue-resident myeloid cells, such as microglia and osteoclasts. CD22 and CD33 (also known as Siglec-3) are expressed in microglia and regulate the clearance of amyloid-β, which is implicated in the development of Alzheimer’s disease, whereas Siglec-15 expressed in osteoclasts regulates bone metabolism. Collectively, these findings strongly suggest that Siglecs represent promising targets for drug discovery to address various intractable diseases and unmet medical needs.