I've stayed in some crazy and different accommodations in my day. Hostels, cheap hotels that rent by the hour, budget rural inns, all the way up to the Four Seasons and Ritz-Carltons (the latter of which, mind you, are pretty rare for me). Fortunately, staying in the Four Seasons or Ritz-Carltons usually gives you the option of the in-room safe, or even the reception vault. But when you're staying in accommodations that don't have these options- which is usually the case for me- how do you keep your valuables safe?
I always keep at least 2 small padlocks in my travel suitcases. They're inexpensive, and usually use a 3- or 4-digit code. An easy code you can plug in for 3-digit padlocks that you won't forget is your telephone's area code. The easiest code you can plug in for 4-digit codes are the last 4 digits of your telephone number or your birth year. I always use these codes, and despite the plethora of 20-some mini-padlocks I have floating around between my suitcases, I can usually get the padlock code within 1 or 2 attempts. When I'm leaving my hotel room for the day, and I have some valuables--e.g. my jewelry or extra cash--I secret them away in some pocket or item of clothing, then lock my suitcase zippers shut with the padlock. It's not foolproof, but it keeps your valuables under some lock and key.
That said, some common sense rules apply. Don't leave valuables, cash, or other things you wouldn't want to lose out in plain sight.Tuck it away, lock it up, or else bring it with you. I also check the windows--if I'm on the ground or second floor, I'll shut and lock the window. If you have to leave money behind, you can always section it off according to bill denominations: e.g. fold some paper around all your twenties, writing the number of bills you have on the paper; do the same for all other denominations before you secrete it away in a preferably padlocked place. It will at least help you keep track of how much money you have stored, rather than guessing, "I THOUGHT I had $200 here but maybe I didn't..." Sometimes the front desk has a vault as I mention above- but keep in mind the convenience factor and how often you need to retrieve your valuables. Finally, always make sure the room door shuts completely behind you and locks when you leave. Then hit the streets and let your mind rest easy knowing you've taken what precautions you can.