Advances in cystic fibrosis (CF) diagnostics and therapeutics have led to improved health and longevity, including increased body weight and decreased malnutrition in people with CF. Highly effective CFTR modulator therapies (HEMT) are associated with increased weight through a variety of mechanisms, accelerating trends of overweight and obesity in the CF population. Higher body mass index (BMI) is associated with improved pulmonary function in CF, yet the incremental improvement at overweight and obese BMIs is not clear. Improvements in pulmonary health with increasing BMI are largely driven by increases in fat-free mass (FFM), and impact of HEMT on FFM is uncertain. While trends toward higher weight and BMI are generally seen as favorable in CF, the increased prevalence of overweight and obesity has raised concern for potential risk of traditional age- and obesity-related comorbidities. Such comorbidities, including impaired glucose tolerance, hypertension, cardiac disease, hyperlipidemia, fatty liver, colon cancer, and obstructive sleep apnea, may occur on top of pre-existing CF-related comorbidities. CF nutrition recommendations are evolving in the post-modulator era to more individualized approaches, in contrast to prior blanket high-fat, high-calorie prescriptions for all. Ultimately, it will be essential to redefine goals for optimal weight and nutritional status to allow for holistic health and aging in people with CF.