Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Awareness of the multisystem concerns that face persons with CF (PwCF) has also continued to be recognized as an important aspect of the burden of the disease. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, an understanding of worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served, ranging from the advances in care in the United States (US) to the challenges of disease recognition and diagnosis in low-and-middle-income countries (LMIC). This review is the third in a three-part CF Year in Review 2020 series, focusing on the multi-system effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three has been split into two individual parts, Part 3A presented here, and Part 3B related to CF specific nutrition and gastrointestinal publications will also be published this year. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.