Lamprey are living representatives of the basal vertebrate agnathan lineage. Many lamprey species are anadromous with a complex life cycle that includes metamorphosis from a freshwater (FW) benthic filter-feeding larva into a parasitic juvenile which migrates to seawater (SW) or (in landlocked populations) large bodies of FW. After a juvenile/adult trophic period that can last up to two years, adults return to rivers and migrate upstream to spawn in FW. Therefore, the osmoregulatory challenges anadromous lamprey face during migrations are similar to those of derived diadromous jawed fishes because lamprey osmoregulate to maintain plasma osmolality at approximately one third SW as well. While in FW, lamprey gills actively take up ions and their kidneys excrete excess water to compensate for passive ion loss and water gain. When in SW, lamprey drink SW and their gills actively secrete excess ions (to compensate for salt loading and dehydration). Nevertheless, lampreys diverged from the rest of the vertebrate lineage more than 500 million years ago, which is reflected in similarities and differences in ionocyte (ion transport cell) ultrastructure and distribution as well as tight junctions in epithelia. The current review discusses recent advances in our understanding of ion transport mechanisms of lamprey with a focus on sea lamprey (Petromyzon marinus) due to the large literature on this species. We emphasize key molecular and cellular mechanisms in osmoregulatory organs (i.e., gill, kidney and gut) and provide insight relative to what is known in other fishes and identify areas where more research is needed.