In and out patients of different age groups are subjected to repeated skin piercing in order to complete the diagnosis, which may cause psychological consequence due to the painful experience or because of phobia fear of needles. We attempt to review most experimental studies investigating the effectiveness of the currently used techniques in reducing the pain related to blood sampling. Venepuncture Methods have been always linked with pain. Nevertheless, it is the most common technique used worldwide. The effectiveness of this methods is mainly depends on the quality of the equipment used as well as the phlebotomist qualification. Polymer microfluidic blood sampling device is a recent innovation that aims to improve the technological ease of blood sampling and to minimize the frequency of venepuncture that the patient exposed to. However this method can only help in-patients. 3D Micro-Needle is the most recent technology that grapes the attention of health care manufacture. Despite the success of this technology in providing less painful alternative for blood sampling, the application of this technology is yet to be adopted in the current practices in hospitals. Dried Blood Spot (DBS) Method is the favourable and the common sampling tool for neonatal screening of various diseases worldwide. This method has been developed into many forms aiming to reduce the pain. Also, laser technology is a method of blood sampling that puncture the fingertip. Till now, this method is mainly used for collecting capillary blood rather than vine blood which limits its applications. In Conclusion, Nowadays and despite the evolution of technology, the need of the health care sector for integrated and effective technology that provides painless blood sampling has not been met yet.