The aim of this systematic review was to examine the clinical cues used by acute care nurses to recognize changes in clinical states of adult medical and surgical patients that occurred as usual consequence of acute illness and treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and checklist were followed. Four databases and reference lists of included studies were searched: from 1,049 studies, 38 were included. There were 26 subjective and 147 objective cues identified; only 6% of all cues described improvements in patients' clinical states. The most common clinical cues used were heart rate, blood pressure and temperature. Many studies (n = 31) focused on only one element of assessment, such as physiological stability, pain, or cognition. There was a paucity of studies detailing the complexity of acute care nurses' assessment practices as they would occur in clinical practice and a disproportionate focus on the objective assessment of deterioration. Studies are needed to understand the full breadth of cues acute care nurses use to recognize clinical change that includes both improvement and deterioration.