Approximately 80 million Americans have limited health literacy, which puts them at greater risk for poorer access to care and poorer health outcomes. To update a 2004 systematic review and determine whether low health literacy is related to poorer use of health care, outcomes, costs, and disparities in health outcomes among persons of all ages. English-language articles identified through MEDLINE, CINAHL, PsycINFO, ERIC, and Cochrane Library databases and hand-searching (search dates for articles on health literacy, 2003 to 22 February 2011; for articles on numeracy, 1966 to 22 February 2011). Two reviewers independently selected studies that compared outcomes by differences in directly measured health literacy or numeracy levels. One reviewer abstracted article information into evidence tables; a second reviewer checked information for accuracy. Two reviewers independently rated study quality by using predefined criteria, and the investigative team jointly graded the overall strength of evidence. 96 relevant good- or fair-quality studies in 111 articles were identified: 98 articles on health literacy, 22 on numeracy, and 9 on both. Low health literacy was consistently associated with more hospitalizations; greater use of emergency care; lower receipt of mammography screening and influenza vaccine; poorer ability to demonstrate taking medications appropriately; poorer ability to interpret labels and health messages; and, among elderly persons, poorer overall health status and higher mortality rates. Poor health literacy partially explains racial disparities in some outcomes. Reviewers could not reach firm conclusions about the relationship between numeracy and health outcomes because of few studies or inconsistent results among studies. Searches were limited to articles published in English. No Medical Subject Heading terms exist for identifying relevant studies. No evidence concerning oral health literacy (speaking and listening skills) and outcomes was found. Low health literacy is associated with poorer health outcomes and poorer use of health care services. Agency for Healthcare Research and Quality.