Although the first in-situ hybridization (ISH) experiments were performed more than two decades ago, it was not until 1987 that the technique was implemented in the study of preimplantation. Since then, several groups have explored the feasibility of using the ISH technique as a diagnostic tool to study the genomic constitution of human preimplantation embryos. Though a fair number of such ISH studies have been published and unravelling of the embryos' genomic secrets proceeds with great strides, there are still many challenges in this area of research. The scope of this review is to outline the research and diagnostic applications of single and multicolour (fluorescence) ISH to study the chromosomal content of human preimplantation embryos and to discuss the implications for human preimplantation genetic diagnosis. Current hybridization techniques are being discussed, including the capabilities and pitfalls of this approach when applied to human preimplantation embryos. Finally, future perspectives for the ISH technique in studying the genomic constitution of preimplantation embryos are reviewed.