Communication issues have been recognized as a contributing factor in the majority of health care errors. Failure to share critical information or concerns with other health care professionals is one type of communication issue, and for years health care professionals have been told to “speak up” when they have information or concerns to address this. What is meant by “speak up” has not been clear, as it has been defined and operationalized in many different ways. A literature review was conducted to explore the meaning of “speak up,” and 187 articles were evaluated for usage of the term speaking up and related synonyms. A mixed methods study was conducted at a large academic medical center, utilizing survey data to identify units with high and low levels of speaking up behaviors and then interviews were conducted with nurses to explore how they define and operationalize speaking up. This led to a description of the phenomenon of speaking up for medical surgical nurses at one hospital. Results from the study and the literature review also indicate that most health care professionals do speak up when they see an issue, indicating we need to examine issues around raising concerns beyond encouraging people to do it. Definitions from the literature and from interviews were examined for similarities and differences and a new definition for speaking up for patient safety is presented. Recommendations for future research, including the need to examine speaking up from the listening side, are discussed.