In the past decade, mid-infrared (MIR) few-cycle lasers have attracted remarkable research efforts for their applications in strong-field physics, MIR spectroscopy, and bio-medical research. Here we present a review of MIR few-cycle pulse generation and amplification in the wavelength range spanning from 2 to ~20 μm. In the first section, a brief introduction on the importance of MIR ultrafast lasers and the corresponding methods of MIR few-cycle pulse generation is provided. In the second section, different nonlinear crystals including emerging non-oxide crystals, such as CdSiP2, ZnGeP2, GaSe, LiGaS2, and BaGa4Se7, as well as new periodically poled crystals such as OP-GaAs and OP-GaP are reviewed. Subsequently, in the third section, the various techniques for MIR few-cycle pulse generation and amplification including optical parametric amplification, optical parametric chirped-pulse amplification, and intra-pulse difference-frequency generation with all sorts of designs, pumped by miscellaneous lasers, and with various MIR output specifications in terms of pulse energy, average power, and pulse width are reviewed. In addition, high-energy MIR single-cycle pulses are ideal tools for isolated attosecond pulse generation, electron dynamic investigation, and tunneling ionization harness. Thus, in the fourth section, examples of state-of-the-art work in the field of MIR single-cycle pulse generation are reviewed and discussed. In the last section, prospects for MIR few-cycle lasers in strong-field physics, high-fidelity molecule detection, and cold tissue ablation applications are provided.