Structural design of genetic studies has progressed over the last decade into the most powerful tool for probing the complex human diseases. There are many different approaches for the identification of genetic risk factors of the complex diseases. New pharmacological therapies may get established by understanding the underpinning of biological genetic effects. We focus here on the applications and strategies that are currently best suitable for genetic studies which provide preliminary genetic information for subsequent statistical analyses. Here we review the basic concept of genetic alterations including monogenic and polygenic characteristics of complex diseases to determine underlying genetic complexity and the most appropriate methods for genetic analysis.