Obviousness under 35 U.S.C. § 103 is the ground on which more patent claims are rejected in prosecution and invalidated in litigation than any other. This guide reconstructs the doctrine from its statutory text and Supreme Court foundations in Graham v. John Deere and KSR v. Teleflex, then dissects exactly what an examiner or challenger must prove to establish a prima facie case: the differences over the prior art, an articulated reason to combine, and a reasonable expectation of success. It works through every substantive rebuttal a patent owner can deploy, from attacking the motivation to combine and negating reasonable expectation of success to teaching away, non-analogous art, change in principle of operation, and the objective indicia of nonobviousness anchored by the nexus requirement. It then translates the doctrine into a layered prosecution response, including claim strategy, declarations under 37 C.F.R. § 1.132, examiner interviews, and the duty of candor. Two original worked hypotheticals and a forum-by-forum comparison of the burdens before the examiner, the PTAB, and the district court round out a research resource written for practitioners, judges, inventors, and business owners alike.