Many ISPs now block inbound port 25, required to receive mail via SMTP. It's quite hard to get an ISP to unblock this. My university wouldn't at all, and I left a laptop under my parents' couch for four years to do it instead. Some time later, Comcast began blocking it as well, and the only way to get it unblocked was to call support, work your way up the phone tree to someone that realized you were talking about inbound rather than outbound (no, this is _not_ a misconfiguration in Outlook), and get them to push a special config to your cable modem, which would be reset whenever another config was auto-pushed, or your modem lost power. You may notice that implies extended downtime when Comcast, my electric service, or my physical operations (read: I unplugged it by accident) suffers a failure.
Many mail servers (e.g. Gmail) require you to have reverse DNS that matches your forward DNS. Getting your ISP to understand what they're asking you to do is... difficult. The last time I changed ISPs, it took about a week to get this done. Comcast batches these updates weekly, and support wanted to double, triple, and quadruple-check that what I was asking for was, indeed, what I was asking for.
There are a bunch of anti-spam measures in effect that use DNS: SPF and DMARC are table stakes for most mail servers (again, e.g. Gmail) to speak to you. I've so far managed to get by without setting up DKIM, but I suspect that's next.
The worst part, by far, is spam blacklists. Many blacklists will already have your IP address listed by policy - you're a _residential IP_, not to be trusted. The Spamhaus PBL, for instance, automatically blocks all Comcast residential IPs. There is nothing you can do about this, and many mail servers will refuse to speak to you if you're on a blacklist.
These days I am paying Comcast an arm and a leg for business-class service, which both gives me unbridled inbound port 25, and also a (luckily!) clean IP on block lists.