The plant basal immune system can detect broadly present microbe-associated molecular patterns (MAMPs, also called PAMPs) and induce defenses, but adapted microbes express a suite of effector proteins that often act to suppress these defenses. Plants have evolved other receptors (R proteins) that detect these pathogen effectors and activate strong defenses. Pathogens can subsequently alter or delete their recognized effectors to avoid defense elicitation, at risk of a fitness cost associated with loss of those effectors. Significant research progress is revealing, among other things, mechanisms of MAMP perception, the host defense processes and specific host proteins that pathogen effectors target, the mechanisms of R protein activation, and the ways in which pathogen effector suites and R genes evolve. These findings carry practical ramifications for resistance durability and for future resistance engineering. The present review uses numerous questions to help clarify what we know and to identify areas that are ripe for further investigation.