Living matters are inadvertently exposed to the highly toxic petroleum hydrocarbon (PH) byproducts. Despite the fact that petroleum-related industry is globally thriving, the health hazard of most hydrocarbons is not well characterized. In human, organs and, sometimes, whole systems such as the nervous system, respiratory, circulatory, immune, reproductive, and endocrine systems are susceptible to PHs depending on the level of exposure. Marine organisms are known to be affected by PHs in various stages. Impacts from lethal to sub-lethal dose of PHs range from habitat destruction, mass mortality, and impaired physiological functions such as reduced feeding, slow growth and development, respiration problems, loss of locomotion, balance, and swimming ability. Bioaccumulation of toxic PHs in food chains in marine environment can be retained for decades and affect plants, animals, and eventually human. This chapter summarizes the PHs toxic effects on living organisms and the potential mechanisms of action based on epidemiological studies.