Melioidosis occurs in both humans and animals following exposure to and infection with Burkholderia pseudomallei in environmental soil and water. However, it should not be seen as a zoonosis, as transmission from animals to humans is exceptionally rare, as is transmission from person to person. In humans, melioidosis and severe disease are usually seen in people with clinical risk factors, most notably diabetes. Similarly, for animals, melioidosis is rarely seen in healthy species native to endemic regions, presumably reflecting co-evolution with B. pseudomallei over millennia. On the other hand, there is differential susceptibility among farm and grazing animals of non-tropical origins. Sheep, alpacas, and camels are especially susceptible, while with good animal husbandry, goats and pigs are farmed in some melioidosis-endemic regions. Melioidosis is seen in companion animals such as dogs and cats, mostly those in poor health. Melioidosis outbreaks have occurred in exotic animals imported into zoos in tropical cities, with tragic consequences for some iconic, critically endangered primate species. The clinical and pathological features seen in animals with melioidosis from natural exposure have been very informative for understanding the spectrum of disease in humans, including different clinical patterns reflecting whether the mode of infection was inhalational, percutaneous, or from ingestion of B. pseudomallei. There is a rapidly expanding global footprint of melioidosis, reflecting both unmasking of endemic disease with improved diagnostics and evolving spread of B. pseudomallei to new receptive locations, attributed to anthropogenic factors. In addition, case numbers in endemic regions have been on the rise and will likely continue to rise because of the triad of increasing numbers of people living with diabetes, environmental disturbance from construction activities with increasing urbanization, and climate change. It is hoped that over the next decade, the global map of the biogeographical boundaries of B. pseudomallei in the environment will be much further refined, enabling targeted support for the specific diagnostics and therapeutics required to minimize mortality from melioidosis.