Despite the technological improvements in orthopedic joint replacement implants, wear and corrosion products associated with the metal components of these implants may result in adverse local tissue and perhaps systemic reactions and toxicities. The current review encompasses a literature review of the local and systemic toxicity studies concerning the effect of CoCrMo wear particles released from wear and corrosion of orthopedic implants and prostheses. Release of metallic debris is mainly in the form of micro- and nano-particles, ions of different valences, and oxides composed of Co and Cr. Though these substances alter human biology, their direct effects of these substances on specific tissue types remains poorly understood. This may partially be the consequence of the multivariate research methodologies employed, leading to inconsistent reports. This review proposes the importance of developing new and more appropriate in-vitro methodologies to study the cellular responses and toxicity mediated by joint replacement wear particles in-vivo.