A search for new physics is performed using events with isolated same-sign leptons and at least two bottom-quark jets in the final state. Results are based on a sample of proton-proton collisions collected at a center-of-mass energy of 8 TeV with the CMS detector and corresponding to an integrated luminosity of 10.5 fb−1. No excess above the standard model background is observed. Upper limits are set on the number of events from non-standard-model sources and are used to constrain a number of new physics models. Information on acceptance and efficiencies is also provided so that the results can be used to confront an even broader class of new physics models.