Microfluidic technologies have several advantages in sample preparation for diagnostics but suffer from the need for an external operation system that hampers user-friendliness. To overcome this limitation in microfluidic technologies, a number of user-friendly methods utilizing capillary force, degassed poly(dimethylsiloxane), pushbutton-driven pressure, a syringe, or a pipette have been reported. Among these methods, the pushbutton-driven, pressure-based method has a great potential to be widely used as a user-friendly sample preparation tool for point-of-care testing or portable diagnostics. In this Perspective, we focus on the pushbutton-activated microfluidic technologies toward a user-friendly sample preparation tool. The working principle and recent advances in pushbutton-activated microfluidic technologies are briefly reviewed, and future perspectives for wide application are discussed in terms of integration with the signal analysis system, user-dependent variation, and universal and facile use.