On an x86-style processor, four bytes represent the ISR's offset and segment address. Without an EI instruction, no interrupt will ever occur. One way of detecting this is to sense the CPU's INTR input pin. If it's asserted all of the time, then generally the chip has all interrupts disabled. It's easy to check this with external peripherals.
Modern peripherals are often incredibly complex.
Motorola's TPU, for example, has an entire book dedicated to its use. Set one bit in one register to the wrong value, and it won't generate the interrupt you are looking for. It's not uncommon to see an interrupt work perfectly once, and then never work again. The only general advice is to be sure your ISR re-enables interrupts before returning. Then look into the details of your processor and peripherals.