BackgroundSocial networking sites (SNSs) have become a pervasive part of modern culture, which may also affect mental health.ObjectiveThe aim of this systematic review was to identify and summarize research examining depression and anxiety in the context of SNSs. It also aimed to identify studies that complement the assessment of mental illness with measures of well-being and examine moderators and mediators that add to the complexity of this environment.MethodsA multidatabase search was performed. Papers published between January 2005 and June 2016 relevant to mental illness (depression and anxiety only) were extracted and reviewed.ResultsPositive interactions, social support, and social connectedness on SNSs were consistently related to lower levels of depression and anxiety, whereas negative interaction and social comparisons on SNSs were related to higher levels of depression and anxiety. SNS use related to less loneliness and greater self-esteem and life satisfaction. Findings were mixed for frequency of SNS use and number of SNS friends. Different patterns in the way individuals with depression and individuals with social anxiety engage with SNSs are beginning to emerge.ConclusionsThe systematic review revealed many mixed findings between depression, anxiety, and SNS use. Methodology has predominantly focused on self-report cross-sectional approaches; future research will benefit from leveraging real-time SNS data over time. The evidence suggests that SNS use correlates with mental illness and well-being; however, whether this effect is beneficial or detrimental depends at least partly on the quality of social factors in the SNS environment. Understanding these relationships will lead to better utilization of SNSs in their potential to positively influence mental health.