To combat the public health threat from emerging coronaviruses (CoV), the development of antiviral therapies with either virus-specific or pan-coronaviral activities is necessary. An important step in antiviral drug development is the screening of potential inhibitors in cell-based systems. The recent emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) necessitates adapting methods that have been used to identify antivirals against severe acute respiratory syndrome coronavirus (SARS-CoV) and developing new approaches to more efficiently screen antiviral drugs. In this article we review cell-based assays using infectious virus (BSL-3) and surrogate assays (BSL-2) that can be implemented to accelerate antiviral development against MERS-CoV and future emergent coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses." © 2013 Elsevier Ltd. All rights reserved.