We can break fatigue into two broad categories, physical and mental. Physical fatigue means your brain is still on and has things for you to do but your body can't keep up. Mental fatigue is more common (except maybe during a seriously long bike ride, run or other punishing exercise) and steps must be taken.
Mental fatigue is not just an annoyance but a sign that your brain is not able to make energy as fast as you are using it. The bottom line is that brain cells will die at an increasing rate. You might see references to brain cells regenerating. I wouldn't count on that happening at a rate that will save you.
The first thing to consider would be psychological reasons. Use local resources to follow up on that as you deem appropriate.
Even a person with a lot of psychological reasons for mental fatigue can have some overlapping physical reasons. Dealing with these physical reasons will make dealing with the psychological reasons much easier.
It helps to have a neurotransmitter profile. For a more complete discussion of testing see Neurotransmitter Testing. Using products that improve excitatory neurotransmitter activity like NeuroScience ExcitaPlus can be a huge help.
Neurotransmitter activity depends on having a steady supply of blood sugar. That is what your brain uses for energy. Taking steps to control hypoglycemia or diabetes will be helpful. Some products that help with fatigue related to hypoglycemia are BetterGenix AdrenalGenix and Integrative Therapeutics Fiber Formula.
You might also take a look at the detox discussion. Go to Detox Basics. A load of heavy metals or organic contaminants will take a toll.
We should also mention that certain foods can contribute to brain problems. Our favorite theme to harp on is gluten sensitivity. I have devoted several articles to this topic. Gluten can stimulate an antibody response that attacks key brain enzymes. For a more complete discussion of see Gluten Resources.