Heavy metal contamination in the aquatic environment is ecologically and economically detrimental, leading to loss of biodiversity and having considerable impacts on human health. Occurrence and accumulation of heavy metals are considered as potential threats to the coastal inhabitants depending on marine resources for food, industry and recreation. In this chapter, four widely used heavy metals, arsenic, cadmium, mercury and lead, are discussed in terms of their toxicological and health impacts on marine environment and humans. Several fishes can bioaccumulate these heavy metals in the tissues, and the heavy metals can be transferred through food chain and can be biomagnified thereafter. Rate of bioaccumulation differs among different species of fishes. Heavy metals are mostly found in the sediments; therefore, benthic species have a higher rate of accumulation rather than pelagic species. Humans are directly exposed to these heavy metals primarily through seafoods; the consequences are evident in several catastrophic breakouts happened previously, like Minamata disaster (in case of mercury) and Itai-Itai disease (in case of cadmium) in Japan. Around a quarter of the human population in South and Southeast Asia are directly or indirectly dependent on fisheries and aquaculture industries and are vulnerable to heavy metal contamination. Several case studies from Asia (South China Sea, Persian Gulf, Mekong Delta, Bay of Bengal) are highlighted in the chapter to show the diverse impacts of heavy metals on marine and estuarine environment. International marine laws regarding waste disposal have been strengthening over the decades to control release and spreading of pollutants. Also, various remediation measures, including physiochemical and biochemical methods, are applied in many cases to remediate heavy metal pollutants in marine and estuarine ecosystems. However, this enormous issue of contamination needs interdisciplinary and sustainable remedial measures, especially collaborative efforts of experts from related disciplines.