School closures, altered access to health services, and economic stress during the COVID-19 pandemic have likely had an impact on the mental and physical well-being of youth worldwide, particularly among those with chronic health conditions (CHCs). A number of challenges and opportunities have emerged during the COVID-19 pandemic for youth with CHCs. Challenges include heightened anxiety, disrupted routines, academic and social stresses associated with school closure, increased risk of domestic violence and abuse, and reduced access to physical and psychosocial support. On the other hand, opportunities include reduced academic and social stress, increased time with families, reduced access to substances, easier access to health care using technology, and opportunities to build resilience. This viewpoint paper highlights both challenges and opportunities for youth with CHCs during the pandemic and offers recommendations for further research and clinical care.