Distiller’s dried grains with solubles (DDGS), a dried residue that remains after the fermentation of grain mash by selected yeasts and enzymes to produce ethanol and carbon dioxide, is currently readily available and less expensive than other conventional protein sources on a per unit protein basis. The nutrient content and nutritional value of DDGS varies with the source and quality of the grains, fermentation time and efficiency, the drying process and the quantity of distiller’s solubles added. In general, corn and wheat DDGS are deficient in lysine and methionine for tilapia, with lysine being the most limiting. Research evaluating the nutritional value of DDGS showed that 20–30% DDGS derived from corn or wheat can be included in tilapia diets without requiring lysine supplementation. With supplementation of lysine, DDGS at levels of 40% or higher can be used without affecting growth performance and feed utilization efficiency. Distiller’s dried grains with solubles also contain yeast, a rich source of beta glucan and nucleotides that have been reported to enhance immunity and disease resistance in fish. Corn DDGS, owing to its high oil content, is rich in linoleic acid and is an excellent source of energy and essential fatty acids for tilapia. High concentrations of xanthophylls present in corn DDGS may impart yellow pigment in fish flesh if included at high levels. Taking into consideration various factors affecting the nutritional value of diets and the quality of pellet and fish products, 15–20% DDGS appears to be optimum in the diets of tilapia.