Students differ in how much they already know about topics within and across their courses. Few studies, however, have examined the relationship between participants' levels of knowledge across topics (i.e., their "domain familiarity") and their learning of information from those topics, their study choices related to those topics, and their subjective self-assessments of their learning about the topics. As such, in two studies we had participants (Study 1, college students; Study 2, Mturk workers) rank their domain familiarity for several to-be-studied domains (e.g., chemistry, history), rate their efficacy and interest in those domains, study and make judgments of learning (JOLs) for facts from each domain, and finally complete a short-answer test over those facts. Participants' efficacy and interest ratings for the topics were linearly related to their topic rankings, as were their recall of and JOLs for facts from those domains. Although the JOLs were consistently overconfident, they were more overconfident for better-known than for lesser-known topics. Participants' study times were not related to their topic rankings (Studies 1 and 2), but participants did use domain familiarity to strategically decide which domains to restudy before the test (Study 2). Participants typically chose to restudy their least-familiar topics, but chose to restudy their best-known topic under extremely limited restudy conditions. As a whole, the results suggest that participants effectively use their domain familiarity as a basis for their JOLs and restudy choices, but to some extent overuse this factor to assess their learning, and underuse it to guide initial study.