The potential of precision spectroscopy as a tool in systematic searches for effects of Lorentz and CPT violation is investigated. Systems considered include hydrogen, antihydrogen, deuterium, positronium, and hydrogen molecules and molecular ions. Perturbative shifts in energy levels and key transition frequencies are derived, allowing for Lorentz-violating operators of arbitrary mass dimensions. Observable effects are deduced from various direct measurements, sidereal and annual variations, comparisons among species, and gravitational responses. We use existing data to place new and improved constraints on nonrelativistic coefficients for Lorentz and CPT violation, and we provide estimates for the future attainable reach in direct spectroscopy of the various systems or tests with hydrogen and deuterium masers. The results reveal prospective sensitivities to many coefficients unmeasured to date, along with potential improvements of a billionfold or more over certain existing results.