The distinctive features of reproduction in squirrels are the lack of allometric influences on the duration of reproductive investment; the strong allometric influences on offspring mass; and a trade-off between number and size of young, suggesting an important developmental component to reproduction. Lengths of gestation and lactation do not vary with body size but neonatal and weaning mass do. Apparently, the major constraint on reproduction in squirrels is not resources per se (food, calories, minerals, or water) but rather the length of time such resources are available. Squirrels adjust growth rate to fit the timing of resource abundance. Within the familial reproductive pattern, arboreal squirrels invest more into reproduction than do ground squirrels. Flying squirrels (Pteromyini) have a larger temporal investment into reproduction but a smaller energetic investment compared with other squirrels. Ground squirrels do not have a distinct reproductive profile, because marmotine and nonmarmotine ground squirrels differ. Marmotine ground squirrels have a small temporal investment and a large energetic investment on a per litter but not on an annual basis. Nonmarmotine ground squirrels have a reproductive pattern similar to that of tree squirrels, a pattern intermediate between marmotines and flying squirrels. Within this locomotor–ecological framework, reproductive patterns differ among subfamilies. Tribes differ in having few (2–4) versus many (4–8) young, and in the relative allocation of investment into gestation versus lactation. Specific environmental influences on reproduction in squirrels occur at lower taxonomic levels within the framework of a broad reproductive pattern set by earlier radiations into particular locomotor and nest-site niches.