The first line of defense in energy efficient operation of your home is its exterior shell; the foundation, walls, and roof. The better constructed relative to insulation and air leaks the shell is, the lower your energy bill will be. It all has to do with the principle that heat flows towards cold. 

How does this impact your home? In the winter, you condition the air inside your home to stay warm. Anywhere there are leaks or areas of heat loss (windows, doors, uninsulated spaces), the warm air will move towards the cold and leave your home. You then need to replace that loss, using more energy. The opposite occurs in the summer when you cool your home. 

According to the United States Department of Energy, a home loses 40% of its energy (https://en.wikipedia.org/wiki/Spray_foam) through infiltration/exfiltration or heat loss/gain. And considering that on average, 50% of a homeowner's energy bill is for heating and cooling, making the shell as tight as possible can have a significant impact on energy costs. Care must be taken to be sure the home is not too tight. Check with local codes on the number of required air changes per hour to keep your home space healthy. 

There are three keys to minimizing this energy loss; insulation, windows/doors (penetrations), and caulking/weather-stripping.