Objective: To systematically evaluate health literacy (HL) interventions in chronic conditions by exploring theoretical perspectives, intervention content and effectiveness. Method: We searched MEDLINE, Cochrane, CINAHL, EMBASE, ERIC, Web of Science and PsycINFO. Standardised systematic review methods were used, and sequences informing our research question were extracted and analysed. The study includes a descriptive summary of the included papers. Results: We included 39 unique interventions, with diabetes and heart disease as the most targeted chronic conditions. Fifty-four percent of papers included a definition of HL, but the studies showed significant hetero-geneity of theoretical underpinnings, modes, measures and content. We identified 23 HL measures, mostly assessing functional HL. The HL interventions were often more complex than the measures indicated. A signif-icant change in HL was found in 28 studies. Study quality was generally poor. Conclusions: Interventions optimizing HL appear important to improve health outcomes in chronic conditions. To ensure cumulative knowledge development of this field we need theory-based interventions, consistency in methods and more tailored and comprehensive measures to capture the interventions' complexity. Practice implications: A more valid understanding of HL interventions and measurements is needed to reach an agreed understanding of their components and intentions.