Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two common betacoronaviruses, which are still causing transmission among the human population worldwide. The major difference between the two coronaviruses is that MERS-CoV is now causing sporadic transmission worldwide, whereas SARS-CoV-2 is causing a pandemic outbreak globally. Currently, different guidelines and reports have highlighted several diagnostic methods and approaches which could be used to screen and confirm MERS-CoV and SARS-CoV-2 infections. These methods include clinical evaluation, laboratory diagnosis (nucleic acid-based test, protein-based test, or viral culture), and radiological diagnosis. With the presence of these different diagnostic approaches, it could cause a dilemma to the clinicians and diagnostic laboratories in selecting the best diagnostic strategies to confirm MERS-CoV and SARS-CoV-2 infections. Therefore, this review aims to provide an up-to-date comparison of the advantages and limitations of different diagnostic approaches in detecting MERS-CoV and SARS-CoV-2 infections. This review could provide insights for clinicians and scientists in detecting MERS-CoV and SARS-CoV-2 infections to help combat the transmission of these coronaviruses.