Applications of HPLC to speciation and determination of mercury compounds in biological, clinical and environmental matrices are reviewed. Almost all modes of HPLC (reverse-phase, ion-pair, ion exchange, micellar) used so far for separation of mercury compounds of interest (Hg²⁺, CH₃Hg⁺, (CH₃)₂Hg, C₂H₅Hg⁺, n-C₃H₇Hg⁺, C₆H₅Hg⁺, etc.) are discussed. Merits of various detection techniques used for mercury and/or organomercurials determination in combination with HPLC and brief description of isolation techniques are presented.