Theoretical, desirable features of second-generation metal-on-metal (MoM) hip prostheses have led to their widespread use. However, the bearing surfaces, consisting of complex cobalt-chromium alloys, are subject to wear and the release of cobalt and chromium (CoCr) nanoparticles. These nanoparticles can reduce cellular viability, induce DNA damage, lead to chromosomal aberrations, and possibly stimulate increased metal hypersensitivity. Clinically, the effects can be both local (soft-tissue reactions) and systemic (arthroprosthetic cobaltism). This review assesses the literature concerning the in vitro and in vivo cytotoxic, genotoxic, and immunotoxic effects of CoCr wear particles, which is increasingly important in view of the large number of MoM arthroplasties performed.