Prepare your smoker and preheat it to 225°F (107°C).
Mix salt, black pepper, paprika, garlic powder, onion powder, and cayenne pepper in a bowl to create the seasoning rub.
Rub the spice mixture evenly over the entire surface of the brisket.
Place the brisket on the smoker grates, fat side up.
Smoke the brisket for about 8-10 hours, or until the internal temperature reaches 195-205°F (90-96°C).
Remove the brisket from the smoker and let it rest for at least 30 minutes before slicing.
Slice the brisket against the grain and serve.