Aquaculture has been developed very rapidly in Vietnam and have a great contribution to global aquaculture production. However, diseases have been one of significant problems for sustainability and profitability of the aquatic farming sector in the country, especially in the Mekong River Delta where is the large areas for aquaculture is located. Emergence and spread of diseases has greatly increased over the past few years along with rapid expansion and intensification of the sector. Although parasites and bacteria have been documented as the most common pathogens, bacterial agents have been identified for the major epizootics in farms where most important aquatic species are cultured. Recently, some new diseases have been reported in cultured aquatic species but the causative agents which are responsible for clinical signs of those diseases have not yet been identified. In this article, major diseases in most commonly cultured species in the Mekong River Delta including catfish, snack-head fish, mudskipper and tilapia will be described and economic losses, rapid diagnositcs and health management in farms of these species will be presented and discussed.