OBJECTIVES:: There is no cure for Alzheimer’s disease (AD). Current treatments only alleviate symptoms and are unable to modify the disease etiology. β-secretase cleaving enzyme inhibitors (BACEi) have been suggested as the promising novel drugs which target the accumulation of β-amyloid plaques in brain–one of the hallmarks of AD pathogenesis. This pipeline assessment review the current status and commercial feasibility of BACEi for AD. METHODS:: Desk research was performed to review the data from clinicaltrials.gov, PubMed, expert’s reviews, analyst’s reports, AD forum and societies, companies’ websites, investor’s presentations, featured press releases from companies, and news to track the most recent updates. Data were analyzed to draw insights. RESULTS:: This analysis revealed 31 total and 20 active BACEi (small-molecules: 13; immunotherapies: 7) across different clinical development stages (Phase-I: 8; Phase-II: 7; Phase-III: 5). Five most optimistic BACEi with potential to breach AD market are verubecestat (MK8931/Merck), AZD3293 (AstraZeneca–Eli Lilly), elenbecestat (E2609/Eisai–Biogen), aducanumab (BIIB037/Biogen), and crenezumab (Roche). Verubecestat is leading the clinical development, with US approval awaited in 2018. AZD3293, elenbecestat and aducanumab have received FDA Fast-Track designation for priority review, with approvals anticipated in 2020–2022. Crenezumab is lagging slightly and approval expected in 2023. CONCLUSIONS:: The total worldwide cost of AD and other dementias is estimated to rise substantially (2015: $818 billion; 2018: $1 trillion; 2030: $2 trillion). Consequently, a tremendous commercial opportunity exists for pharmaceutical/biotech companies developing BACEi. Given the high failure of pipeline AD drugs: >99.6% during 2002–2012 and the very recent failure of Eli Lilly’s solanezumb in late-stage Phase-III trial, it is entirely possible that none of the five BACEi mentioned succeed. Being a very risky business, the market penetration of BACEi as a new era of Alzheimer’s disease-modifying therapies will remain elusive or turn into reality is yet to be witnessed.