Pinctada fucata Gould 1850 was first commercially cultivated in Japan in the early 1920s. Japan dominated this market until the proliferation of Akoya viral disease (AVD) in 1996. Since that time the Japanese industry has struggled. In 2000, Japanese production of Akoya pearls represented only 13% of the total world market value. A number of investigations into this downturn have concluded that the proliferation of AVD was a result of stress associated with increasing urbanization and industrialization. This relationship between environmental stress and altered immunological activity is well documented in a number of oyster species. The decline in Japanese pearl production has led to interest in Akoya cultivation in Australia. Commercial Akoya pearl oyster ventures are now in operation in the Australian states of New South Wales, Queensland and Western Australia. The development of a robust and lucrative Akoya pearl industry in Australia will rely on the cultivation and maintenance of healthy oysters. Oyster health is associated with immunological status, which can be jeopardized by both stress and disease. This review details the relationship between the oyster immune system, environmental stress and disease outbreaks in the genus Pinctada, with implications for P. fucata and the fledgling Australian industry.