Diabetes is an increasing public health problem, and insulin is the mainstay for treatment of type 1 diabetes. In type 2 diabetes treatment, insulin therapy is used after oral or other injectable agents become inadequate to achieve glycemic control. Despite the advances in insulin therapy, management of diabetes remains challenging. Numerous studies have reported low adherence and persistence to insulin therapy, which acts as a barrier to successful glycemic control and diabetes management. The aim of this targeted review article is to provide an overview of adherence and persistence to insulin therapy in people with diabetes and to discuss the impact of the emergence of a new connected ecosystem of increasingly sophisticated insulin pens, glucose monitoring systems, telemedicine, and mHealth on diabetes management. With the emergence of a connected diabetes ecosystem, we have entered an era of advanced personalized insulin delivery, which will have the potential to enhance diabetes self-management and clinical management. Early systems promise to unlock the potential to address missed or late bolus insulin delivery, which should help to address non-adherence and non-persistence. Over time, improvements in this ecosystem have the potential to combine insulin data with previously missing contextualized patient data, including meal, glucose, and activity data to support personalized clinical decisions and ultimately revolutionize insulin therapy.