I agree with a lot of what was already posted. I imagine there could be concern about your ability to pass training in a timely manner after so long out of the cockpit. Twenty years is a very long time to not use the technical knowledge you learned and also not maintain the motor skills. Plus, as was pointed out, you're dealing with learning a lot of new technology as well as regulatory changes.
Something that wasn't pointed out is that long periods out of aviation make an employer question your dedication to a flying career, particularly since you abandoned it for so long. How do they know you won't bail out on them after a brief period of time after they've wasted resources on hiring and training you? You're a little late to the party.
Reading between the lines from your posting, you're probably about 50 years old and you haven't flown since you were about 30 years old. Yes, you could probably get current and might be able to get hired by a regional, because they're getting more desperate for pilots now and your lack of currency is less of an issue than it would be in other times. But why would you want to do that to yourself unless you have no other career options? (Didn't you find a good career to support your family for the past 20 years?) At age 50 and with your lack of recent flight time, you'll spend several years at a regional with low pay and poor working conditions before you'd even be considered for hire at a major. By then you're in your late 50's with only a few years left before mandatory retirement at 65, if your medical even holds up that long. Quite a few pilots get disqualified before then. The majors may not touch you with less than a decade to work for them and even if they do, you'd spend your entire major career at probationary or 8-year or less pay as a First Officer, maybe on reserve with little control over your schedule. Remember, the airline life is 24/7/365 -- no weekends or holidays. And seniority is everything at the airlines. When you're eternally junior, it's not much of a life, even if the pay is decent.
I don't know what your other options are, but I'd think twice before going down this path in my 50's. I'm probably a little older than you and can't fathom just starting out as a regional FO at my age.