OBJECTIVE: To synthesize the current evidence for subcutaneous hydration and medication infusions from systematic reviews and to assess their methodological quality. INTRODUCTION: Peripheral intravascular cannula/catheter insertion is a common invasive procedure for administering fluids and medications. Venous depletion is a growing concern for several patient populations. Subcutaneous access for the administration of isotonic solutions and medications is an alternative; however, vascular access assessment and planning guidelines rarely consider this route. METHODS: Systematic review of systematic reviews (PROSPERO CRD42018046504). We searched 6 databases published in English language from 1990 to June 2020, identifying subcutaneous infusions an alternate route for fluids or medication. Methodological quality was evaluated using AMSTAR 2 criteria and data for mechanisms of infusion and outcomes related to effectiveness, safety, efficiency and acceptability extracted. The Johanna Briggs Institute's grades of recommendation informed the strength of recommendation. RESULTS: The search yielded 1042 potential systematic reviews; 922 were excluded through abstract and duplicate screen. Of the remaining articles, 94 were excluded, and 26 were included. Overall, evidence is strong for recommending subcutaneous hydration infusions for older adults, weak for pediatric patients and inconclusive for palliative patients. There is strong evidence for 10 medications; weak evidence supporting 28 medications; however, there are eight medications with inconclusive evidence to make a recommendation and four medications not appropriate for subcutaneous delivery. CONCLUSION: Subcutaneous access should be considered alongside intravenous therapy for hydration in older adults, and several medications. There are additional benefits in terms of ease of use and cost-effectiveness of this mode. Inclusion of subcutaneous access in clinical guidelines may promote uptake of this route to help preserve vessel health of vulnerable patients. Further high-quality research is needed to inform subcutaneous infusion therapy in a variety of populations (including pediatrics and palliative care) and medications and clarifying the mechanism of delivery.