Stable isotope systematics of phosphatic (vertebrate) and carbonate (invertebrate) fossils are reviewed, emphasizing external vs. biological controls on isotope compositions and their variation. External controls include elevation and isotopic lapse rates, temperature, atmospheric circulation patterns, aridity, and changes to precipitation seasonality, e.g., development of monsoons. Biological controls include temperature regulation and temperature-dependent biological activity, water balance, behavior, and rates of hard-part secretion and maturation. Some key factors include what sources of water an animal samples, how those sources respond isotopically to elevation, and the isotopic sensitivity of a biologic tissue to environmental changes. General research design criteria are enumerated, including numbers of fossils and analyses required, as well as uncertainties in the interpretability of isotopic shifts. Isotope zoning from fossil teeth and shells from the Indian foreland demonstrate comparable seasonal monsoon signals at ~11 Ma vs. today, implying a high and broad plateau at that time. Mean isotope compositions of fossil teeth from the lee of the Cascade Range, central Oregon, show a pronounced decrease in δ18O initiating ~7 Ma, signaling topographic rise associated with impingement of Basin and Range extension on the arc. Mean compositions and zoning in fossil shells from the northern Rocky Mountains indicate high elevations and topographic relief in the late Cretaceous and early Paleogene. Paleoaltimetry will principally benefit from better estimates of temperature, because temperature lapse rates are less variable than isotopic lapse rates, and because the combination of temperature and isotopic studies may help distinguish between local isotopic changes and distal ones caused by catchment or rain shadow effects.