Tuberculosis remains the major public health concern worldwide responsible for about 1.6 million deaths and 0.3 million co-infected with Human immunodeficiency virus (HIV) annually. Mycobacterium is the causative agent of tuberculosis infection and is transmitted principally through air when an infected person coughs, talks, sneezes etc. This infection can be diagnosed using different Microbiological, Molecular and Immunological techniques including, sputum smear microscopy, sputum culture, nucleic-acid amplification test (NAAT), genotyping assay, tuberculin skin test (TST), interferon-gamma release assay (IGRAs) etc. These techniques vary in sensitivity and specificity as well as the ease with which they are carried out. World Health Organization (WHO) encourages the use of techniques that are sensitive, patient-friendly, and those which produce accurate results in any clinical setting world-wide. Hence, this review highlights smear microscopy and incorporation of more rapid and sensitive diagnostic techniques such as GeneXpert, IGRAs and urinary antigen analysis in clinical setting in the detection of Mycobacterium. These techniques show high sensitivity, are less time consuming do not require a repeat for a single result, some are able to differentiate latent and active TB infections, and have the capacity to be used to screen people unable to expectorate. This review encourages the incorporation of smear microscopy, GeneXpert, IGRAs, urinary antigen analysis into routine laboratory diagnosis especially in high TB burden countries. It is believed that high level of sensitivity and less time used in producing results display by these techniques will yield reduction in mortality rate, decline in static nature of TB status and possibly zero TB 2020 proposed by WHO.