Cadmium (Cd) is a naturally occurring ubiquitous element of environmental concern. Concentrations of Cd in the geosphere are generally low except for enrichment in association with Zn, Pb, and Cu sulfidic ore deposits, as well as some phosphate rock formations. Uses of Cd include batteries, pigments, stabilizers, coatings, and some alloys. The toxicity of Cd to aquatic species depends on speciation, with the free ion, Cd2+ concentration being proportional to bioavailability. Toxicity is reduced via complexation of Cd2+ by inorganic and organic anions and through competitive interactions between Ca2+ and Cd2+ for uptake sites. Cd2+ acute toxicity involves disruption of ion homeostasis, particularly Ca, but also Na and Mg. Uptake at the fish gill occurs apically via a lanthanum-sensitive voltage-independent epithelial Ca2+ channel located in the mitochondria-rich chloride cells and basolaterally via Ca-ATPase and an Na/Ca exchanger. Chronic exposure also involves ionoregulatory disturbance and disruptions to growth, reproduction, the immune system, endocrine, development, and behavior; gill, liver, and kidney histopathologies also develop. Cadmium accumulates primarily in the kidney and liver. Accumulation has been linked to oxidative damage, which may be a mechanism linking the many different chronic effects. Uptake across gastrointestinal and olfactory surfaces is not well understood but evidence exists for gut Cd uptake via L-type voltage-gated Ca2+ channels, a high-affinity Ca2+-ATPase and a divalent metal transporter-1. Acclimation to chronic Cd exposure involves a variety of defense and detoxification processes, such as antioxidants (catalase), metallothionein, glutathione, and heat shock proteins, making the development of bioaccumulation-based impact prediction models for Cd a challenge.