There is a growing biomedical interest in hemocyanin, the giant oxygen transporter glycoprotein of some mollusks, due to their remarkable therapeutic effect as non-specific immunostimulant: they trigger both the innate and adaptive arms of the mammals immune system. Nowadays, hemocyanin is used as alternative therapy of Bacillus Calmette-Guèrin (BCG) to preventing superficial bladder tumor recurrence, with far fewer side effects, in addition to their widespread use as carrier to develop antibodies against peptides and haptens (drugs, hormones, toxins, and peptides, mainly) and as carrier-adjuvant by new vaccines against cancer, drug addiction and against old and emerging infectious diseases. It is also used in the diagnosis of parasitic diseases as schistosomiasis. The hemocyanin from the Californian gastropod Megathura crenulata, known as keyhole limpet hemocyanin (KLH), has been used for over thirty years for the above purposes. More recently, hemocyanin from the Chilean mollusk Concholepas concholepas (CCH) has proved to be a reliable alternative to KLH, either as carrier protein, and as likely alternative for the treatment of superficial bladder cancer, as support recent preclinical studies. Interestingly, although KLH and CCH differ significantly in their origin and structure, we found that both hemocyanins immunomodulate in a similar way the innate and adaptive arms of mammals’ immune response: they are potent inducers of Th1-type cellular and humoral immunity. We present here a comprehensive analysis with information on the KLH and CCH structure, their most relevant biomedical applications, and some of the immunological mechanism proposed to explain their notable immunomodulatory effects, in the aim of contributing to the medical knowledge of these fascinating proteins.