Abstract: One-dimensional substrates such as textile fibers and threads offer an excellent opportunity to realize sensors, actuators, energy harvesters/storage, microfluidics, and advanced therapies. A new generation of wearable devices made from smart threads offer ultimate flexibility and seamless integration with the human body and the garments that adorn them. This article reviews the state of the art in thread-based wearable devices for monitoring human activity and performance, diagnoses and manages medical conditions, and provides new and improved human–machine interfaces. In the area of new and improved human–machine interfaces, it discusses novel computing platforms enabled using thread-based electronics and batteries/capacitors. For physical activity monitoring, a review of wearable devices using strain sensing threads is provided. Thread-based devices that can monitor health from biological fluids such as total analysis systems, wearable sweat sensing patches, and smart sutures/smart bandages are also included. The article concludes with an outlook on how fibers and threads are expected to impact and revolutionize the next generation of wearable devices. Knowledge gaps and emerging opportunities are presented.