State-of-the-art polypyrrole nanofiber-based nanoarchitectonics can be generally fabricated by electrospinning, interfacial polymerization and reactive template methods. Even though analogous nanofiber morphologies and nanofibrous network architectures can be obtained by these methods, the structural details and structural complexities may alter significantly as different synthesis methods are applied. For the electrospinning technique, on one hand, nanofibers can be directly obtained by spinning polypyrrole-containing dope solutions; on the other, the electrospun nanofiber mats can be used as templates to direct the nanofiber formation; a two-step fabrication process, including the electrospinning of polymer nanofiber mats and deposition of polypyrrole on the polymer nanofibers' surface, is generally employed. By tuning the electrospinning parameters, the composition, diameter, morphology, and alignment of the as-obtained electrospun nanofiber mat can be effectively controlled, which may allow the fabrication of polypyrrole nanofibers with sophisticated nanostructures and nanoarchitectures. Interfacial polymerization is capable of generating polypyrrole nanofibers without templates. It is speculated that the protonation and re-orientation of polypyrrole at the oil–water interface may decoil the polymer chains and transform them into more extended conformations, while the charged polymer chains more easily diffuse into the water phase and form a stable dispersion. Different from electrospinning, the reactive templates may drive the formation of polypyrrole nanofibers through either redox or protonation mechanisms. Nanofibers with different curvatures, compositions, and architectures can be obtained by using different types of reactive template in a simple, fast, environment-friendly and one-step manner. A wide range of applications have been demonstrated by the polypyrrole nanofiber-based nanoarchitectonics, including cell culture, tissue engineering, neural stimulation, energy storage, and organic electronics.