Let's see how these questions can be applied to your genealogy research.
WhoWho are you looking for? Since genealogy and family history research is tied to the people in the family this is one of those obvious questions. Are you looking for a spouse? Maybe a sibling?
WhatWhat are you looking for concerning the person from the Who question? Are you looking for a name or a date? Are searching for a specific document such as a birth, marriage, or death registration? Possibly the What you are looking for is more specific such as "What did the Who die from?"
WhenWhen might the person have lived? Figuring out the time period can help you determine what sorts of documents exist in order to answer the What. Did the Who live in the years prior to civil registration? If so, then looking for a birth registration document (a What) might be a futile exercise since now you may have to look for a family bible or baptism document as the What. You might just have to refine the What question.
WhereWhere did the person live? Knowing Where the Who lived can often help you answer the What question since the documents are often created where someone lived. The Where can be the name of the country, province or state, county, township, or town. Yet here we can run in to a little problem. Borders are man-made and due to war or other disputes the borders can move. Even names of places can change. If you are looking for someone that lived in Kitchener, Ontario, Canada from the late 1800s to the mid 1900s then you might be out of luck if you only look for them in "Kitchener" since before 1916 that place was called "Berlin". The When can help you determine the borders and names of the places for the time in question. Then you will know where to search.
WhyWhy did something happen? Once the first four questions are dealt with often most people stop and move on to the next Who. Yet the Why can often lead you learn more about the history of an area or the driving forces in your ancestor's life. "Why did the Who die of the What in Where in the When year?" can lead to finding out more about the 1918 flu pandemic and the effects it had on the soldiers and civilian populations. Maybe you are tracing a relative that in one census they are living in Scotland and the next census they are found in New Jersey, USA. Your question could be "Why did they leave their family and go across the ocean?" Answering that can help bring your family to life.
HowHow did it happen? I'm not talking about the birds and the bees here. Instead this question often is important when trying to figure out the Why. If your ancestor travelled from one coast to another look at how they made the journey. Was it by ship or by rail? Depending on the time and mode of travel that could indicate a certain amount of wealth or social standing. If they were well off at a particular time in their life yet when they died they were a pauper then looking at the social and economic history of the time may shed some light into their life.
Answer these questions for each person in your family tree and you will find that their lives will start coming to life for you.
[Corrected the new name for Berlin, Ontario thanks to some observant readers.]