In situ Hybridization (ISH), since its introduction in 1969 by Gall and Pardue has found multiple uses in molecular morphology due to its unique capability of visualizing nucleic acid sequences without altering the cell's cytological, chromosomal or histological integrity. Fluorescence in situ Hybridization (FISH) has established itself as a variation of the traditional hybridization process whereby the probes utilized are a fluorescently labeled and produce bright clear signals upon detection. FISH is involved in localizing and exploring chromosomal, genetic and genomic aberrations that are often directly correlated to disease causation and progression. This technique is used as an essential tool not only in research laboratories, but also in prognostics, diagnostics and disease monitoring in medicine. In the past decade, there have appeared multiple modifications to traditional FISH technology allowing a wider variety of practical applications. Some of the latest innovative techniques discussed in this review paper are Forward and Reverse Chromosome Painting, Chromosome in situ suppression hybridization (CISS), Multicolor FISH, Chromosomal bar coding, Micro-FISH, In situ Hybridization to mRNA, in-cell RT-PCR, Fluorescence immunophonotyping and interphase cytogenetics as tool for investigation of neoplasmas (FICTION), Primed in situ DNA synthesis (PRINS), Fiber-FISH, FISHES, and Comparative genomic hybridization (CGH). This paper provides a brief overview of FISH and the techniques exploiting FISH modifications as well as their evaluation and discussion of practical applications.