We provide an extensive review of ammonia fiber expansion (AFEX) pretreatment from a techno-economical and environmental sustainability perspective. A brief historical perspective on concentrated ammonia-based pretreatments is provided followed by a detailed overview of the AFEX process and its physicochemical impact on lignocellulosic plant cell walls. AFEX is unique in terms of leaving biomass composition virtually intact after pretreatment, unlike other aqueous pretreatments. The impact of AFEX pretreatment on enzymatic digestibility and microbial fermentability for a diverse selection of feedstocks is reviewed. The utility of using transgenic plants as feedstocks for an AFEX process are highlighted. Recent developments of the AFEX process (e.g., extractive vs. non-extractive AFEX) are discussed along with a focus on commercialization efforts to develop cheap, hybrid AFEX reactors with in-built, low-cost ammonia recovery systems. Integration of the AFEX process into a regional biomass processing depot is discussed along with its ramifications on plant protein extraction, animal feed production, on-site enzyme production, and biomass fractionation. Finally, we discuss various techno-economic and life-cycle analysis modeling efforts that have centered on systems employing the AFEX process.